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851.
852.
Sequencing and analysis of an Irish human genome   总被引:1,自引:0,他引:1  

Background

Recent studies generating complete human sequences from Asian, African and European subgroups have revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from a population of interest due to its relative geographical isolation and genetic impact on further populations, we extend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence.

Results

Using sequence data from a branch of the European ancestral tree as yet unsequenced, we identify variants that may be specific to this population. Through comparisons with HapMap and previous genetic association studies, we identified novel disease-associated variants, including a novel nonsense variant putatively associated with inflammatory bowel disease. We describe a novel method for improving SNP calling accuracy at low genome coverage using haplotype information. This analysis has implications for future re-sequencing studies and validates the imputation of Irish haplotypes using data from the current Human Genome Diversity Cell Line Panel (HGDP-CEPH). Finally, we identify gene duplication events as constituting significant targets of recent positive selection in the human lineage.

Conclusions

Our findings show that there remains utility in generating whole genome sequences to illustrate both general principles and reveal specific instances of human biology. With increasing access to low cost sequencing we would predict that even armed with the resources of a small research group a number of similar initiatives geared towards answering specific biological questions will emerge.  相似文献   
853.
Mammalian translation initiation factor 3 (eIF3) is a multisubunit complex containing at least 12 subunits with an apparent aggregate mass of approximately 700 kDa. eIF3 binds to the 40S ribosomal subunit, promotes the binding of methionyl-tRNAi and mRNA, and interacts with several other initiation factors to form the 40S initiation complex. Human cDNAs encoding 11 of the 12 subunits have been isolated previously; here we report the cloning and characterization of a twelfth subunit, a 28-kDa protein named eIF3k. Evidence that eIF3k is present in the eIF3 complex was obtained. A monoclonal anti-eIF3a (p170) Ig coimmunoprecipitates eIF3k with the eIF3 complex. Affinity purification of histidine-tagged eIF3k from transiently transfected COS cells copurifies other eIF3 subunits. eIF3k colocalizes with eIF3 on 40S ribosomal subunits. eIF3k coexpressed with five other 'core' eIF3 subunits in baculovirus-infected insect cells, forms a stable, immunoprecipitatable, complex with the 'core'. eIF3k interacts directly with eIF3c, eIF3g and eIF3j by glutathione S-transferase pull-down assays. Sequences homologous with eIF3k are found in the genomes of Caenorhabitis elegans, Arabidopsis thaliana and Drosophila melanogaster, and a homologous protein has been reported to be present in wheat eIF3. Its ubiquitous expression in human tissues, yet its apparent absence in Saccharomyces cerevisiae and Schizosaccharomyces pombe, suggest a unique regulatory role for eIF3k in higher organisms. The studies of eIF3k complete the characterization of mammalian eIF3 subunits.  相似文献   
854.
Eleven microsatellite loci were developed in the swordfish, Xiphias gladius, to examine population structure. Loci were amplified in samples from two geographically distant populations (Ecuador and Mediterranean Sea). Observed heterozygosity ranged from 0.150 to 0.960. Most loci conformed to Hardy–Weinberg expectations with the exception of locus Xg‐59, which had a heterozygote deficit caused probably by null alleles. Locus Xg‐402 did not show significant divergence between the populations. The remaining nine loci showed statistically significant spatial heterogeneity (genic differentiation) between the two populations, making them useful for future studies of population structure in swordfish.  相似文献   
855.
中英两国有着完全不同的历史。在英国,工业发展始于18世纪,随着财富的积累,迅速席卷了英伦三岛。由于对因此而造成的环境破坏没有得到重视,污染物不可避免地沉积下来,当时流行的一句话是“哪有烟尘,哪就有金钱”。尽管在某种程度上也曾提出过早期的  相似文献   
856.
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Differentiation of adipocytes is accompanied by secretion of molecules stimulating angiogenesis in vivo and endothelial cell growth and motility in vitro. We demonstrate that the angiogenic and motility-stimulating activities secreted by adipocytes are separable from the endothelial cell mitogenic activity by fractionation of adipocyte-conditioned medium. The major differentiation-dependent angiogenic molecule was purified and identified by GCMS as 1-butyryl-glycerol (monobutyrin). Monobutyrin levels increase at least 200-fold during adipocyte differentiation and represent a major fraction of the total angiogenic activity. Synthetic monobutyrin shows the same spectrum of biological activities as the adipocyte-derived factor: stimulation of angiogenesis in vivo and microvascular endothelial cell motility in vitro, with no effect on endothelial cell proliferation. Angiogenesis is stimulated at doses as low as 20 pg when tested in the chick chorioallantoic membrane assay. These results strongly suggest that monobutyrin is a key regulatory molecule in an angiogenic process linked to normal cellular and tissue development.  相似文献   
859.
The subcellular distribution of Met and S-adenosylmethionine (AdoMet) metabolism in plant cells discloses a complex partition between the cytosol and the organelles. In the present work we show that Arabidopsis contains three functional isoforms of vitamin B(12)-independent methionine synthase (MS), the enzyme that catalyzes the methylation of homocysteine to Met with 5-methyltetrahydrofolate as methyl group donor. One MS isoform is present in chloroplasts and is most likely required to methylate homocysteine that is synthesized de novo in this compartment. Thus, chloroplasts are autonomous and are the unique site for de novo Met synthesis in plant cells. The additional MS isoforms are present in the cytosol and are most probably involved in the regeneration of Met from homocysteine produced in the course of the activated methyl cycle. Although Met synthesis can occur in chloroplasts, there is no evidence that AdoMet is synthesized anywhere but the cytosol. In accordance with this proposal, we show that AdoMet is transported into chloroplasts by a carrier-mediated facilitated diffusion process. This carrier is able to catalyze the uniport uptake of AdoMet into chloroplasts as well as the exchange between cytosolic AdoMet and chloroplastic AdoMet or S-adenosylhomocysteine. The obvious function for the carrier is to sustain methylation reactions and other AdoMet-dependent functions in chloroplasts and probably to remove S-adenosylhomocysteine generated in the stroma by methyltransferase activities. Therefore, the chloroplastic AdoMet carrier serves as a link between cytosolic and chloroplastic one-carbon metabolism.  相似文献   
860.
Duplicate staining of human metaphase chromosomes, first with Giemsa followed by silver, revealed the presence of two small silver-stained bodies not seen in the Giemsa stained metaphases. Similar bodies were subsequently found in the metaphases of several animal groups. The size, structure, spatial relationships to the nucleus, behavior throughout the cell cycle, and apparent universal presence of these bodies suggest that they are either centrioles or associated centriolar structures. These centriole-bodies can be seen throughout the cell cycle, even in hypotonically spread C-metaphase chromosome plates. The silver stain procedure allows enough resolution to distinguish parent and daughter centriole-bodies at interphase, thus permitting visualization of the replication, maturation and separation stages of these bodies with the light microscope.  相似文献   
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